Use of EF5 to Measure the Oxygen Level in Tumor Cells of Patients Undergoing Surgery or Biopsy for Newly Diagnosed Supratentorial Malignant Glioma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00430079

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

This clinical trial is using EF5 to measure the oxygen level in tumor cells of patients undergoing surgery or surgery biopsy for newly diagnosed supratentorial malignant glioma. Diagnostic procedures using the drug EF5 to measure the oxygen level in tumor cells may help in planning cancer treatment

Condition or Disease	Intervention/Treatment	Phase
Adult Anaplastic Astrocytoma Adult Anaplastic Ependymoma Adult Anaplastic Oligodendroglioma Adult Diffuse Astrocytoma Adult Ependymoma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Mixed Glioma Adult Myxopapillary Ependymoma Adult Oligodendroglioma Adult Pilocytic Astrocytoma Adult Pineal Gland Astrocytoma Adult Subependymoma	Drug: etanidazole Procedure: conventional surgery Other: pharmacological study Other: laboratory biomarker analysis	N/A

Detailed Description

PRIMARY OBJECTIVES:

Determine the presence and pattern of etanidazole derivative EF5 binding with tumor, based on image and cellular analyses, in patients undergoing surgery or biopsy for newly diagnosed supratentorial malignant gliomas.
Determine the level of EF5 binding within histologic subtypes of this tumor in these patients.

Compare the relationship between hypoxia and clinical outcomes in patients with glioblastoma multiforme (GBM) vs non-GBM.

Determine the spatial relationships between EF5 binding and tumor tissue biomarkers and pathophysiologic processes (e.g., necrosis, proliferation, and apoptosis) in these patients.
Determine the relationship between EF5 binding and Eppendorf needle electrode measurements in these patients.

OUTLINE:

Patients receive etanidazole derivative EF5 IV over 1-2½ hours once within 1-2 days before surgical resection or biopsy. Tumor tissue, normal tissue, and/or tumor-infiltrated lymph node samples are collected during surgery and stained for biological markers. Fluorescent immunohistochemistry techniques are used to determine the presence, distribution, and levels of EF5 binding.

Patients are followed at 1 month, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within 1½-2 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Assessment of Hypoxia in Malignant Gliomas Using EF5

Study Start Date :

Jul 1, 2001

Actual Primary Completion Date :

Sep 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Diagnostic (etanidazole) Patients receive etanidazole derivative EF5 IV over 1-2½ hours once within 1-2 days before surgical resection or biopsy. Tumor tissue, normal tissue, and/or tumor-infiltrated lymph node samples are collected during surgery and stained for biological markers. Fluorescent immunohistochemistry techniques are used to determine the presence, distribution, and levels of EF5 binding.	Drug: etanidazole Given IV Other Names: 2-nitro-imidazole derivative SR-2508 Procedure: conventional surgery Undergo surgery Other Names: surgery, conventional Other: pharmacological study Correlative studies Other Names: pharmacological studies Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Diagnostic (etanidazole)

Drug: etanidazole

Given IV

Other Names:

2-nitro-imidazole derivative

SR-2508

Procedure: conventional surgery

Undergo surgery

Other Names:

surgery, conventional

Other: pharmacological study

Correlative studies

Other Names:

pharmacological studies

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Time to local recurrence [Time from study entry (EF5 administration) to local recurrence, assessed up to 3 years]

Secondary Outcome Measures

Time to death [Up to 3 years]
Presence and pattern of EF5 binding in newly diagnosed brain masses by IHC analyses [At 48 hours after EF5 administration]
Levels of EF5 binding within histological subtypes of SMG [At baseline, at 1 hour, and the time of surgery]
Relationship between hypoxia and clinical outcomes (i.e., time to local recurrence and survival) [Up to 3 years]
Time to local recurrence and survival will be estimated by the method of Kaplan and Meier.
Association between EF5 binding and Eppendorf needle electrode measurements in brain masses [Up to 3 years]
The correlation between median oxygen pressure (pO2) by Eppendorf electrode measurement and percent of maximal signal in tumors (by EF5 binding) will be assessed by Pearson's correlation coefficient.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed and/or clinical and imaging evidence of a new brain mass that is likely to be a supratentorial malignant glioma
Clinical condition and physiologic status indicative of debulking surgery or biopsy as standard initial therapy
Performance status - Karnofsky performance status 60-100%
WBC greater than 2,000/mm^3
Platelet count greater than 90,000/mm^3
Creatinine less than 2.0 mg/dL
No significant cardiac condition that would preclude study therapy
No symptomatic congestive heart failure
No unstable angina pectoris
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 1 month after study completion
Weight no greater than 130 kilograms
No grade 3 or 4 peripheral neuropathy
No other invasive malignancy within the past 3 years that is likely to cause a solitary supratentorial metastasis
No uncontrolled concurrent illness, medical condition, psychiatric illness, or social situation that would preclude study participation
At least 6 months since prior chemotherapy
Concurrent corticosteroid therapy allowed
At least 6 months since prior radiotherapy to lesion or site of lesion
At least 6 months since prior surgery to lesion or site of lesion except incisional or core biopsy
Concurrent anticonvulsant therapy allowed
No other concurrent investigational agents